Efficacy and Safety of BCD-063 and Copaxone-Teva in Patients With Relapsing-Remitting Multiple Sclerosis

International, Multicentre, Double-blind, Placebo-controlled, Comparative, Randomized Study to Compare Efficacy and Safety of the Generic Drug BCD-063 (CJSC "BIOCAD", Russia) and Copaxone®-Teva ("Teva Pharmaceutical Industries Limited", Israel) in Patients With Relapsing-remitting Multiple Sclerosis

The objective of the clinical study of the medicinal product for medical use: to compare efficacy and safety of the generic drug BCD-063 and Copaxone®-Teva in patients with relapsing-remitting multiple sclerosis.

Period of the clinical study of the medicinal product for medical use: from June 10, 2013 to March 23, 2016.

Number of patients, involved into the study of the medicinal product for medical use: 158 patients.

Study Overview

• Status: Completed
• Conditions: Relapsing-remitting Multiple Sclerosis
• Intervention / Treatment: Drug: Placebo; Drug: BCD-063; Drug: Copaxone-Teva

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Previously diagnosed multiple sclerosis (MS, McDonald criteria 2005);
• Disease more, than 1 year prior to inclusion;
• Presence of 1 relapse previously OR at least 1 Gd+ lesion in T1 regimen;
• EDSS 0-5,5;
• Absence of exacerbations for 4 weeks prior to inclusion;
• Readiness of patients (both genders) to use reliable methods of contraception (at least 1 barrier method in combination with: spermicides, intrauterine device/oral contraceptives)

Exclusion Criteria:

• Secondary progressive and primary progressive forms of multiple sclerosis;
• Other diseases (except multiple sclerosis), which may affect the assessment of the severity of the symptoms of the underlying disease: mask, amplify, modify the symptoms of the underlying disease or cause the clinical manifestations and changes in the data of laboratory and instrumental methods of investigation similar to those of multiple sclerosis;
• Any acute or chronic infection in the acute stage;
• Verified HIV, hepatitis B and C, syphilis;

• Metabolic abnormalities (disorders), which manifest themselves as:

  1. raising the general level of creatinine is more than 2 times over the upper limit of the normal range;
  2. increase in transaminases (ALT, AST) or gamma-glutamyltransferase more than 2.5 times over the upper limit of the normal range;
• Violation of bone marrow function as reducing the total number of leukocytes <3000 /mcl, or a platelet count <125000 /mcl, hemoglobin concentration reduction, or <100 g / l;
• EDSS> 5,5 points;
• Liver disease in the stage of decompensation;
• Congestive heart failure, or not controlled by a drug therapy angina or arrhythmia;
• Pregnancy, breast-feeding or planned pregnancy during the study period;
• Use of any time prior to study any drug for modifying multiple sclerosis: interferon beta-1a, interferon beta-1b, glatiramer acetate, azathioprine, corticosteroids and immunomodulators (except for treating exacerbations corticosteroids), drugs and monoclonal antibodies, cytotoxic and / or immunosuppressive drugs, including, but not limited to drugs: mitoxantrone, cyclophosphamide, cyclosporine, fingolimod, cladribine; or total lymphoid irradiation system;
• System (IV, oral) corticosteroids within 30 days prior to the screening visit;
• Intolerance or allergy to glatiramer acetate, mannitol or other components of the BCD-063 preparations or Copaxone®-Teva;
• History of drug addiction, alcoholism and abuse of drugs;
• Contraindications to MRI (gadolinium allergic to or intolerant of closed spaces, any renal failure, which may interfere with the removal of gadolinium - an acute or chronic renal failure);
• Any malignancies, including in anamnesis;
• Vaccination within 4 weeks prior to study entry (prior to randomization);
• Participation in any other clinical trial within 30 days prior to screening or simultaneous participation in other clinical trials;
• Previous participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BCD-063 (glatiramer acetate); Subcutaneous injection of glatiramer acetate BCD-063 subcutaneously every day	Drug: BCD-063; Other Names: glatiramer acetate
ACTIVE_COMPARATOR: Copaxone-Teva (glatiramer acetate); Subcutaneous injection of glatiramer acetate Copaxone-Teva subcutaneously every day	Drug: Copaxone-Teva; Other Names: glatiramer acetate
PLACEBO_COMPARATOR: Placebo; Subcutaneous injection of mannitol 40 mg, water for injections till 1 ml, every day	Drug: Placebo; Other Names: mannitol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Unique Activity lesions	Cumulative Unique Activity (CUA) detected by MRI	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual relapse rate	Relapse per patient per year	48 weeks
Proportion of patients without relapses	Proportion of patients without confirming relapses with magnetic resonance imaging (MRI)	48 weeks
Changing in volume of hypointense T1 lesions		48 weeks
Changing in volume of T2 lesions		48 weeks
Amount of new or extended lesions in T2 regimen		48 weeks
Patients proportion without lesions		48 weeks
T1 lesions amount		48 weeks
Expanded Disability Status Scale dynamics	Expanded Disability Status Scale (EDSS) scale count at 24th and 48th week, comparing count at week 24 to week 48 for each group	Week 24, Week 48
Progression on Multiple Sclerosis Functional Composite scale comparing to the baseline		48 weeks
Risk of relapse	Relative Risk Ratio for relapse in each group	48 weeks
Time till the first relapse		48 weeks
Multiple Sclerosis Functional Composite scale dynamics	Multiple Sclerosis Functional Composite (MSFC) scale count at 24th and 48th week, comparing count at week 24 to week 48 for each group	24, 48 weeks

Collaborators and Investigators

• Sponsor: Biocad
• Investigators: Study Director: Roman A. Ivanov, PhD, Biocad

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (ACTUAL): November 1, 2015
• Study Completion (ACTUAL): November 1, 2015

Study Registration Dates

• First Submitted: April 19, 2016
• First Submitted That Met QC Criteria: April 25, 2016
• First Posted (ESTIMATE): April 27, 2016

Study Record Updates

• Last Update Posted (ACTUAL): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 8, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Equivalence; BCD-063; Copaxone-Teva
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Adjuvants, Immunologic; Mannitol; Glatiramer Acetate; (T,G)-A-L
• Other Study ID Numbers: BCD-063-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No